CRELD1-Associated Neurodevelopmental Disorder: Three New Individuals from Unrelated Families
Jessica Archer1, Shuxiang Goh2, Christina Miteff3
1Hunter Genetics, Waratah, NSW 2298, Australia.
Genes
|August 28, 2025
Summary
Biallelic variants in the CRELD1 gene are linked to a distinct neurodevelopmental disorder. This study expands the known clinical and genetic spectrum of CRELD1-associated neurodevelopmental disorders.
Area of Science:
- Genetics
- Neurodevelopmental Biology
- Molecular Medicine
Background:
- CRELD1 encodes a cell adhesion molecule.
- Initially linked to atrioventricular septal defects (AVSDs).
- Recently associated with syndromic and non-syndromic neurodevelopmental disorders (NDDs).
Purpose of the Study:
- To describe individuals with compound heterozygous CRELD1 variants.
- To delineate shared and divergent clinical features.
- To expand the phenotypic and genetic spectrum of CRELD1-associated NDDs.
Main Methods:
- Exome sequencing to identify CRELD1 variants.
- Clinical and genetic data review.
- Genotype-phenotype correlation analysis.
Main Results:
- Three unrelated patients with compound heterozygous CRELD1 variants were identified.
- All patients presented with developmental delay, intellectual disability, seizures, hypotonia, and dysmorphic features.
- Phenotypic heterogeneity was observed, with no cardiac or immunological abnormalities in the studied patients.
Conclusions:
- Biallelic CRELD1 variants cause a distinct autosomal recessive neurodevelopmental disorder.
- Findings reinforce genotype-phenotype correlations for CRELD1.
- The study broadens the clinical and genetic spectrum of this emerging syndrome.
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